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Penta-block copolymer microspheres: Impact of polymer characteristics and process parameters on protein release
Authors:Minh-Quan Le  Fabien Violet  Cédric Paniagua  Xavier Garric  Marie-Claire Venier-Julienne
Institution:1. MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, 4 rue Larrey, 49933 Angers Cedex 9, France;2. Institut des Biomolecules Max Mousseron (IBMM), UMR5247, Université de Montpellier, CNRS, ENSCM, Faculté de Pharmacie, 15 Avenue Charles Flahault, 34093 Montpellier, France
Abstract:Here, we aimed to develop protein loaded microspheres (MSs) using penta-block PLGA-based copolymers to obtain sustained and complete protein release. We varied MS morphology and studied the control of protein release. Lysozyme was used as a model protein and MSs were prepared using the solid-in-oil-in-water emulsion solvent extraction method. We synthesized and studied various penta-block PLGA-based copolymers. Copolymer characteristics (LA/GA ratio and molecular weight of PLGA blocks) influenced MS morphology. MS porosity was influenced by process parameters (such as solvent type, polymer concentration, emulsifying speed), whereas the aqueous volume for extraction and stabilizer did not have a significant effect. MSs of the same size, but different morphologies, exhibited different protein release behavior, with porous structures being essential for the continuous and complete release of encapsulated protein. These findings suggest strategies to engineer the morphology of MSs produced from PLGA-based multi-block copolymers to achieve appropriate release rates for a protein delivery system.
Keywords:DCM  dichloromethane  DMF  dimethyl formamide  DSC  differential scanning calorimetry  EE  encapsulation efficiency  FDA  food and drug administration  FITC  fluorescein isothiocyanate  GA  glycolic acid  HCl  hydrochloric acid  LA  lactic acid  MS  microsphere  NMR  nuclear magnetic resonance  PEG  polyethylene glycol  PLGA  P188  poloxamer 188  SEC  size exclusion chromatography  SEM  scanning electron microscopy  S/O/W  solid-in-oil-in-water  TRIS  tris(hydroxymethyl)aminomethane  Protein sustained release  Penta-block copolymer  Morphology  Microencapsulation
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